Progress in understanding the molecular basis of cell adhesion should provide a firm ground work for uncovering the defect in cell adhesion that results in malignancy. Our laboratory and other investigators have recently isolated and characterized several different proteins that mediate cell-to-cell contact. Further investigation of these cell adhension proteins should provide a clear understanding of cell adhesion at the molecular level. Once the normal mechanisms of cell adhesion are defined, it should be possible to identify the defect that results in malignancy. During the proposed grant period, we will analyze a collagen dependent cell attachment protein (c-CAP) that mediates the attachment of mammalian cells to collagen. We will investigate the conditioned medium of several cell lines for the presence of new forms of c-CAP by means of a new technique, term bioautography. Bioautography will also be employed to compare the cell surface and serum forms of c-CAP as well as to detect c-CAP molecules which have been structurally modified by enzymatic or chemical treatment. The ability of cells to respond to c-CAP during different stages of the cell cycle will be studied. In addition, the effect of c-CAP on cell migratory behavior will be studied. In oder to study the cell membrane receptor for c-CAP, genetic complementation analysis of non-adhesive fibroblast mutants will be carried out. Hybridomas, that secrete monoclonal antibodies to c-CAP, will be isolated. Progress in studying the biochemistry and physiological role of cell adhesion proteins should advance our knowledge of the normal mechanisms governing tissue morphogenesis and the abnormal changes that result in the spread cancer.